Spatial and molecular profiling of the mononuclear phagocyte network in classic Hodgkin lymphoma.

Classic Hodgkin lymphoma (cHL) has a rich immune infiltrate, which is an intrinsic component of the neoplastic process. Malignant Hodgkin Reed-Sternberg cells (HRSCs) create an immunosuppressive microenvironment by the expression of regulatory molecules, preventing T-cell activation. It has also been demonstrated that mononuclear phagocytes (MNPs) in the vicinity of HRSCs express similar regulatory mechanisms in parallel, and their presence in tissue is associated with inferior patient outcomes. MNPs in cHL have hitherto been identified by a small number of canonical markers and are usually described as tumor-associated macrophages. The organization of MNP networks and interactions with HRSCs remains unexplored at high resolution. Here, we defined the global immune-cell composition of cHL and nonlymphoma lymph nodes, integrating data across single-cell RNA sequencing, spatial transcriptomics, and multiplexed immunofluorescence. We observed that MNPs comprise multiple subsets of monocytes, macrophages, and dendritic cells (DCs). Classical monocytes, macrophages and conventional DC2s were enriched in the vicinity of HRSCs, but plasmacytoid DCs and activated DCs were excluded. Unexpectedly, cDCs and monocytes expressed immunoregulatory checkpoints PD-L1, TIM-3, and the tryptophan-catabolizing protein IDO, at the same level as macrophages. Expression of these molecules increased with age. We also found that classical monocytes are important signaling hubs, potentially controlling the retention of cDC2 and ThExh via CCR1-, CCR4-, CCR5-, and CXCR3-dependent signaling. Enrichment of the cDC2-monocyte-macrophage network in diagnostic biopsies is associated with early treatment failure. These results reveal unanticipated complexity and spatial polarization within the MNP compartment, further demonstrating their potential roles in immune evasion by cHL.

Coblation intracapsular tonsillectomy: A cohort study of NHS practice in England using Hospital Episode Statistics.

OBJECTIVES: To identify paediatric intracapsular Coblation tonsillectomy procedures from routine administrative data in England, and determine their safety. DESIGN: Retrospective observational cohort study of four ENT centres using routine data from Hospital Episode Statistics (HES). SETTING: Acute NHS trusts in England conducting exclusively intracapsular Coblation tonsillectomy. PARTICIPANTS: Children (≤16 years old) undergoing bilateral intracapsular Coblation tonsillectomy. MAIN OUTCOME MEASURES: Number of procedures, readmissions for pain, readmissions for bleeding and requirement for additional surgery for regrowth. RESULTS: A total of 5525 procedures were identified. The median patient age was 4 (IQR 2-5). In-hospital complications occurred in 1%, with 0.1% returning to theatre for arrest of primary tonsil bleeding. Almost half of the procedures were conducted as a day-case (44%), with only a small proportion staying in hospital more than one night (7%). Within 28 days, 1.2% of patients were readmitted with bleeding, 0.7% with infection and 0.3% with pain; 0.2% of patients required return to theatre for control of secondary haemorrhage. Longitudinal follow-up has found that revision tonsil surgery is 0.3% at 1 year (n = 4498), 1.1% at 2 years (n = 2938), 1.7% at 3 years (n = 1781), 1.9% at 4 years (n = 905) and 2.2% at 5 years (n = 305). CONCLUSIONS: Intracapsular coblation tonsillectomy safety outcomes in this study show primary and secondary bleeding rates and emergency return to theatre rates are lower than all tonsillectomy techniques reported in the National Prospective Tonsillectomy Audit and also lower than previously published Hospital Episode Statistics analysis of tonsillectomy procedures.

Lingual Alveolar Soft Part Sarcoma in a 1-Year-Old Infant: Youngest Reported Case With Characteristic ASPSCR1-TFE3 Fusion.

Alveolar soft part sarcoma (ASPS) is an exceptionally rare non-rhabdomyosarcomatous soft tissue sarcoma (NRSTS), characterized by the translocation t(X;17) p(11.2;q25). This translocation results in the chimeric ASPSCR1-TFE3 transcription factor which drives tumorigenesis. Complete surgical resection is crucial in allowing a successful outcome in these cases. Here, we describe an 11-month-old female infant who presented with a well-circumscribed lesion of the tongue, with the clinical and radiologic appearances of an infantile hemangioma. This led to an initial plan for surveillance management. However, the mass continued to enlarge and the lesion was therefore biopsied when the infant was 17 months old. Histology showed plump epithelioid tumor cells, in many places lining pseudoalveolar spaces. Occasional Pas-D inclusions were present in the cytoplasm. Immunostaining showed nuclear positivity for TFE-3. Real-time quantitative polymerase chain reaction testing confirmed the presence of ASPSCR1-TFE3 fusion transcripts, characteristic of the translocation t(X;17) p(11.2;q25) observed in ASPS. This represents the youngest reported ASPS case with a confirmed molecular diagnosis. Complete surgical resection was undertaken and a surveillance imaging schedule implemented. This case highlights the need for regular review of the initial diagnosis and the importance of multidisciplinary discussion and early biopsy where the clinical course does not follow that expected for the putative (nonhistologically confirmed) diagnosis.

Coblation intracapsular tonsillectomy in a paediatric tertiary centre: Revision surgery rates over a nine-year period.

OBJECTIVES: Coblation intracapsular tonsillectomy (ICT) is increasingly being used in the paediatric population because of the rapid recovery and low rates of complications associated with it. There is, however, a risk of symptomatic regrowth with this technique. The objective of our study is to establish the rate of, and risks for, revision surgery over time in a major tertiary referral centre with a large cohort of paediatric Coblation ICT cases. METHODS: A retrospective review of all children (0-19 years) undergoing Coblation ICT from April 2013 to June 2022 was undertaken, using electronic databases and clinical records. Post-operative follow up was reviewed and revision cases were subsequently identified and examined. Statistical analysis was performed using a Chi-Squared test. RESULTS: 4111 patients underwent Coblation ICT during the studied period, with or without concomitant adenoidectomy. Of these, 135 (3.3 %) required revision tonsil surgery, primarily for recurrence of initial symptoms; two patients required two consecutive revision procedures (137 revision procedures in total). Eight-eight (n = 88) (64 %) of these were revised with a repeat Coblation ICT procedure and 49 (36 %) with bipolar diathermy extracapsular tonsillectomy (ECT) of remnant tonsil tissue. The revision rates after Coblation ICT declined steeply on a year-on-year basis since the commencement of this technique (from 10.6 % early on, to 0.3 % at the end of the study period P<0.001). A significantly higher revision rate was noted in children below the age of two at the time of primary surgery, compared to those older than two years of age (P<0.001). CONCLUSIONS: This study demonstrates real-world departmental revision rates over a nine-year period from the technique's commencement of use. With Coblation ICT, symptomatic re-growth occurs rarely, but may be clinically significant, with higher rates of recurrent symptoms seen in children under two years of age at the time of primary surgery. The revision rate apparently drops over time in parallel with overall experience of surgeons and formalised training.

Synchronous airway lesions in children with severe, progressive and atypical laryngomalacia - Experience of a UK tertiary referral centre.

OBJECTIVES: Laryngomalacia is the commonest cause of stridor in the paediatric population. Whilst usually self-limiting, studies have suggested that the presence of synchronous airway lesions (SALs) might be associated with more severe clinical presentation and additional morbidity. However, evidence in the literature is scarce, contributing to controversy regarding the appropriate investigation and management of children with laryngomalacia. The aim of this study was to explore the prevalence, clinical significance and risk factors of SALs in children with severe, progressive and atypical laryngomalacia symptoms. METHODS: Retrospective analysis of the records of all paediatric patients diagnosed with laryngomalacia in a UK tertiary referral centre, over a 2-year period, was undertaken. Data on demographics, comorbidities, management and presence of SALs were collected. RESULTS: The study included 130 patients with laryngomalacia. Seventy-eight patients required investigation with microlaryngobronchoscopy (MLB), based on clinical presentation. SALs were identified in 22 patients (28.2%), 6 of which (7.7%) required surgical intervention. The commonest airway lesions included tracheomalacia, bronchomalacia and subglottic stenosis. A correlation between the presence of neurodevelopmental conditions in children and SALs was noted (p value < 0.05). The presence of SALs was not associated with sex, gestational age at birth or other medical comorbidities. CONCLUSION: The results of this study allow professionals to counsel families about the utility of MLB in children with severe, progressive and atypical laryngomalacia symptoms and inform management pathways for clinicians not working in airway centres. We support the clinical practice that progressive, atypical or severe laryngomalacia symptoms should prompt consideration of an MLB, to identify potential synchronous airway lesions. Furthermore, we propose that a higher index of suspicion and more thorough investigation might be indicated in children with neurodevelopmental disorders.

Simultaneous cochlear implantation in children: the Great Ormond Street experience.

OBJECTIVES: To analyse the surgical aspects and safety of bilateral simultaneous cochlear implantation in children. METHODS: A retrospective case series at a tertiary paediatric centre in the United Kingdom. Surgical times, analgesia and antiemetic use, and complications were analysed for the first 25 bilateral simultaneous cochlear implants performed at Great Ormond Street Hospital for Children between September 2007 and December 2009. These were compared with a consecutive group of sequentially implanted children whose second implant was performed during the same period. RESULTS: Total time for simultaneous implantation was significantly less than the cumulative time required for sequential implantation (P < 0.05). In addition, the number of paracetamol, non-steroidal anti-inflammatory, and antiemetic doses was significantly less for simultaneous implantation than for sequential implantation (P < 0.001). Furthermore, the number of doses of analgesia and antiemetic required for simultaneous implantation were no higher than for single-side surgery (P > 0.05). No difference in complication rates was seen between the groups. DISCUSSION: Bilateral simultaneous cochlear implantation in children is safe and results in a reduction in total theatre time when compared with the cumulative time required for sequential implantation. Simultaneous implantation also reduces total analgesia and antiemetic requirements and length of stay to levels comparable with single-side implantation.